title: Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects.
abstract: BACKGROUND
  Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy.
  
  
  METHODS
  Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment.
  
  
  RESULTS
  Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ≥20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed.
  
  
  CONCLUSIONS
  Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes.
authors.affiliation: Breast Oncology Program, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive, Med Inn Building C450, Ann Arbor, MI 48109-5843, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Henry
authors.forename: H-P
authors.initials: HP
authors.lastname: Chan
authors.forename: J
authors.initials: J
authors.lastname: Dantzer
authors.forename: C P
authors.initials: CP
authors.lastname: Goswami
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: T C
authors.initials: TC
authors.lastname: Skaar
authors.forename: J M
authors.initials: JM
authors.lastname: Rae
authors.forename: Z
authors.initials: Z
authors.lastname: Desta
authors.forename: N
authors.initials: N
authors.lastname: Khouri
authors.forename: R
authors.initials: R
authors.lastname: Pinsky
authors.forename: S
authors.initials: S
authors.lastname: Oesterreich
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.forename: L
authors.initials: L
authors.lastname: Hadjiiski
authors.forename: S
authors.initials: S
authors.lastname: Philips
authors.forename: J
authors.initials: J
authors.lastname: Robarge
authors.forename: A T
authors.initials: AT
authors.lastname: Nguyen
authors.forename: A M
authors.initials: AM
authors.lastname: Storniolo
authors.forename: D A
authors.initials: DA
authors.lastname: Flockhart
authors.forename: D F
authors.initials: DF
authors.lastname: Hayes
authors.forename: M A
authors.initials: MA
authors.lastname: Helvie
authors.forename: V
authors.initials: V
authors.lastname: Stearns
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000627:therapeutic use; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D000077289:Letrozole; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D001141:Aromatase; C561410:CYP19A1 protein, human; C056516:exemestane